Key information relevant to the recruitment process for the
overall study, such as dates of the recruitment period and locations

A total of 240 participants with metastatic and/or unresectable GIST whose disease had progressed despite prior treatments with at least imatinib and sunitinib were screened; 199 were randomized. Patients must have shown objective disease progression or intolerance to imatinib, as well as disease progression while on sunitinib treatment.

Pre-Assignment Details

Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

Participants were randomized in a 2:1 ratio to receive either regorafenib (133 patients) or placebo (66 patients). Randomization was stratified according 3rd vs. 4th line of therapy (at least 50% of patients were to be 3rd line), and geographical region (Asia vs.rest of world).

Reporting Groups

Description

Regorafenib (Stivarga, BAY73-4506)

Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks

Placebo First, Then Option of Open Label Regorafenib Treatment

Double blind phase: participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks. Open Label phase: participants on placebo who switched to Regorafenib, received Regorafenib 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

No text entered.

Reporting Groups

Description

Regorafenib (Stivarga, BAY73-4506)

Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks

Placebo

Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks

Total

Total of all reporting groups

Baseline Measures

Regorafenib (Stivarga, BAY73-4506)

Placebo

Total

Number of Participants
[units: participants]

133

66

199

Age
[units: Years]Mean (Standard Deviation)

58.2
(12.5)

58.1
(13.9)

58.2
(12.9)

Gender
[units: Participants]

Female

48

24

72

Male

85

42

127

ECOG Performance Status (PS)]
[1][units: Participants]

PS 0

73

37

110

PS 1

60

29

89

PS 2

0

0

0

Missing

0

0

0

Prior anti-cancer drug group
[2][units: Participants]

3rd line

74

39

113

4th line and beyond

59

27

86

[1]

ECOG = Eastern cooperative oncology group PS levels are 0 (Fully active, able to carry on all pre-disease performance), 1 (ambulatory and able to carry out work of a light or sedentary), 2 (Ambulatory and capable of all selfcare but unable to carry out any work activities), 3 (Capable of only limited selfcare, confined to bed or chair more than 50% of awake time), 4 (Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair) and 5 (death).

Overall Survival (OS) was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their date of last contact. Since the median value could not be estimated due to censored data, the number of participants with events is presented.

Time Frame

From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately one year

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Full Analysis Set (FAS)

Reporting Groups

Description

Regorafenib (Stivarga, BAY73-4506)

Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks

Placebo

Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks

Measured Values

Regorafenib (Stivarga, BAY73-4506)

Placebo

Number of Participants Analyzed
[units: participants]

133

66

Overall Survival
[units: Percentage of participants]

21.8

25.8

Statistical Analysis 1 for Overall Survival

Groups [1]

All groups

Method [2]

Log Rank

P Value [3]

0.198896

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

No text entered.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

stratified

[3]

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

No text entered.

Statistical Analysis 2 for Overall Survival

Groups [1]

All groups

Method [2]

Regression, Cox

Hazard Ratio (HR) [3]

0.772

95% Confidence Interval

0.423 to 1.408

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

Hazard ratio and its 95% CI was based on stratified Cox Regression Model

[2]

Other relevant method information, such as adjustments or degrees of freedom:

stratified

[3]

Other relevant estimation information:

regorafenib over control

3. Secondary:

Time to Progression (TTP) [ Time Frame: From randomization of the first subject until until date of database cutoff (26 Jan 2012); study duration approximately 1 year ]

Disease Control Rate (DCR) was defined as the percentage of subjects whose best response was Complete Response (CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).), Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.), or Stable Disease (SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.) according to RECIST v1.1 criteria. SD had to be maintained for at least 12 weeks from the first demonstration of that rating. Results are based on central evaluation.

Time Frame

From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Full Analysis Set (FAS)

Reporting Groups

Description

Regorafenib (Stivarga, BAY73-4506)

Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks

Placebo

Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks